A marked regional heterogeneity in blood flow at the level of large arterioles or small arteries is present within single skeletal muscles both in the dog and in the rabbit. A corresponding regional heterogeneity in metabolic activity could explain this phenomenon. We studied the correlation between regional blood flow and regional uptake of glucose within single muscles. Blood flow and glucose uptake were measured using the microsphere technique and the deoxyglucose method, respectively. Blood flow and glucose uptake were determined in 0.25-g regions from resting and stimulated muscles in anesthetized rabbits. Under resting conditions, no correlation between regional blood flow and regional glucose uptake (P greater than 0.05, 12 muscles) was observed. During stimulation, regional blood flow was positively correlated (0.4 less than r less than 0.6, P less than 0.05, 12 muscles) with regional glucose uptake. The coefficients of variation for regional blood flow and regional glucose uptake averaged approximately 0.35 and 0.23, respectively, both at rest and during stimulation. Specific fiber type distributions could not explain either the regional heterogeneity in blood flow or in glucose uptake. We conclude that regional blood flow within single skeletal muscles is not strongly linked to regional uptake of glucose. Both variables show considerable heterogeneity.